scholarly journals Mechanism of duration perception in artificial brains suggests new model of attentional entrainment

2019 ◽  
Author(s):  
Ali Tehrani-Saleh ◽  
J. Devin McAuley ◽  
Christoph Adami
Keyword(s):  
In Silico ◽  
Cognitive Theory ◽  
Human Subjects ◽  
Extended Model ◽  
Psychometric Characteristics ◽  
Neural Basis ◽  
New Model ◽  
Auditory Oddball ◽  
The Brain ◽  
Artificial Brains

While cognitive theory has advanced several candidate frameworks to explain attentional entrainment, the neural basis for the temporal allocation of attention is unknown. Here we present a new model of attentional entrainment that is guided by empirical evidence obtained using a cohort of 50 artificial brains. These brains were evolved in silico to perform a duration judgement task similar to one where human subjects perform duration judgements in auditory oddball paradigms1. We found that the artificial brains display psychometric characteristics remarkably similar to those of human listeners, and also exhibit similar patterns of distortions of perception when presented with out-of-rhythm oddballs. A detailed analysis of mechanisms behind the duration distortion in the artificial brains suggests that their attention peaks at the end of the tone, which is inconsistent with previous attentional entrainment models. Instead, our extended model of entrainment emphasises increased attention to those aspects of the stimulus that the brain expects to be highly informative.

Ligand and Structure-based Modeling of Passive Diffusion through the Blood-Brain Barrier

2018 ◽  
Vol 25 (9) ◽  
pp. 1073-1089 ◽  
Author(s):  
Santiago Vilar ◽  
Eduardo Sobarzo-Sanchez ◽  
Lourdes Santana ◽  
Eugenio Uriarte
Keyword(s):  
Blood Brain Barrier ◽  
In Silico ◽  
Passive Diffusion ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
Different Types ◽  
The Brain

Background: Blood-brain barrier transport is an important process to be considered in drug candidates. The blood-brain barrier protects the brain from toxicological agents and, therefore, also establishes a restrictive mechanism for the delivery of drugs into the brain. Although there are different and complex mechanisms implicated in drug transport, in this review we focused on the prediction of passive diffusion through the blood-brain barrier. Methods: We elaborated on ligand-based and structure-based models that have been described to predict the blood-brain barrier permeability. Results: Multiple 2D and 3D QSPR/QSAR models and integrative approaches have been published to establish quantitative and qualitative relationships with the blood-brain barrier permeability. We explained different types of descriptors that correlate with passive diffusion along with data analysis methods. Moreover, we discussed the applicability of other types of molecular structure-based simulations, such as molecular dynamics, and their implications in the prediction of passive diffusion. Challenges and limitations of experimental measurements of permeability and in silico predictive methods were also described. Conclusion: Improvements in the prediction of blood-brain barrier permeability from different types of in silico models are crucial to optimize the process of Central Nervous System drug discovery and development.

The Brain In Silico

2021 ◽  
pp. 1-36
Author(s):  
Joaquin Marro ◽  
Joaquin J. Torres
Keyword(s):  
In Silico ◽  
The Brain

scholarly journals Monitoring Migraine Cycle Dynamics with an Easy-to-Use Electrophysiological Marker—A Pilot Study

Sensors ◽  
2018 ◽  
Vol 18 (11) ◽  
pp. 3918 ◽  
Author(s):  
Goded Shahaf ◽  
Pora Kuperman ◽  
Yuval Bloch ◽  
Shahak Yariv ◽  
Yelena Granovsky
Keyword(s):  
Pilot Study ◽  
Stress Level ◽  
Event Related Potentials ◽  
Healthy Controls ◽  
Preliminary Results ◽  
Auditory Oddball ◽  
Control Subjects ◽  
Related Potentials ◽  
Auditory Oddball Task ◽  
The Brain

Migraine attacks can cause significant discomfort and reduced functioning for days at a time, including the pre-ictal and post-ictal periods. During the inter-ictsal period, however, migraineurs seem to function normally. It is puzzling, therefore, that event-related potentials of migraine patients often differ in the asymptomatic and inter-ictal period. Part of the electrophysiological dynamics demonstrated in the migraine cycle are attention related. In this pilot study we evaluated an easy-to-use new marker, the Brain Engagement Index (BEI), for attention monitoring during the migraine cycle. We sampled 12 migraine patients for 20 days within one calendar month. Each session consisted of subjects’ reports of stress level and migraine-related symptoms, and a 5 min EEG recording, with a 2-electrode EEG device, during an auditory oddball task. The first minute of the EEG sample was analyzed. Repetitive samples were also obtained from 10 healthy controls. The brain engagement index increased significantly during the pre-ictal (p ≈ 0.001) and the ictal (p ≈ 0.020) periods compared with the inter-ictal period. No difference was observed between the pre-ictal and ictal periods. Control subjects demonstrated intermediate Brain Engagement Index values, that is, higher than inter-ictal, yet lower than pre-ictal. Our preliminary results demonstrate the potential advantage of the use of a simple EEG system for improved prediction of migraine attacks. Further study is required to evaluate the efficacy of the Brain Engagement Index in monitoring the migraine cycle and the possible effects of interventions.

scholarly journals Multifaceted origins of sex differences in the brain

2016 ◽  
Vol 371 (1688) ◽  
pp. 20150106 ◽  
Author(s):  
Margaret M. McCarthy
Keyword(s):  
Sex Differences ◽  
State Of The Art ◽  
Human Subjects ◽  
Special Issue ◽  
Molecular Analyses ◽  
The Past ◽  
Current State ◽  
Biological Variable ◽  
Males And Females ◽  
The Brain

Studies of sex differences in the brain range from reductionistic cell and molecular analyses in animal models to functional imaging in awake human subjects, with many other levels in between. Interpretations and conclusions about the importance of particular differences often vary with differing levels of analyses and can lead to discord and dissent. In the past two decades, the range of neurobiological, psychological and psychiatric endpoints found to differ between males and females has expanded beyond reproduction into every aspect of the healthy and diseased brain, and thereby demands our attention. A greater understanding of all aspects of neural functioning will only be achieved by incorporating sex as a biological variable. The goal of this review is to highlight the current state of the art of the discipline of sex differences research with an emphasis on the brain and to contextualize the articles appearing in the accompanying special issue.

Variables That Influence the Generation of Random Sequences: An Update

1997 ◽  
Vol 84 (2) ◽  
pp. 627-661 ◽  
Author(s):  
Peter Brugger
Keyword(s):  
Short Term Memory ◽  
Human Subjects ◽  
Complete Suppression ◽  
Random Generation ◽  
Short Term ◽  
Random Sequences ◽  
Potential Applications ◽  
Basic Experiments ◽  
The Brain ◽  
Relevant Work

This article updates Tune's 1964 review of variables influencing human subjects' attempts at generating random sequences of alternatives. It also covers aspects not included in the original review such as randomization behavior by patients with neurological and psychiatric disorders. Relevant work from animal research (spontaneous alternation paradigm) is considered as well. It is conjectured that Tune's explanation of sequential nonrandomness in terms of a limited capacity of short-term memory can no longer be maintained. Rather, interdependence among consecutive choices is considered a consequence of an organism's natural susceptibility to interference. Random generation is thus a complex action which demands complete suppression of any rule-governed behavior. It possibly relies on functions of the frontal lobes but cannot otherwise be “localized” to restricted regions of the brain. Possible developments in the field are briefly discussed, both with respect to basic experiments regarding the nature of behavioral nonrandomness and to potential applications of random-generation tasks.

scholarly journals Proteome-Wide Mapping and Reverse Vaccinology Approaches to Design a Multi-Epitope Vaccine against Clostridium perfringens

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1079
Author(s):  
Fahad M. Aldakheel ◽  
Amna Abrar ◽  
Samman Munir ◽  
Sehar Aslam ◽  
Khaled S. Allemailem ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Epitope Vaccine ◽  
Ifn Gamma ◽  
Cellular Immune Responses ◽  
Medical Control ◽  
Food Borne ◽  
Food Borne Illness ◽  
Cellular Immune ◽  
The Brain

C. perfringens is a highly versatile bacteria of livestock and humans, causing enteritis (a common food-borne illness in humans), enterotoxaemia (in which toxins are formed in the intestine which damage and destroy organs, i.e., the brain), and gangrene (wound infection). There is no particular cure for the toxins of C. perfringens. Supportive care (medical control of pain, intravenous fluids) is the standard treatment. Therefore, a multiple-epitope vaccine (MEV) should be designed to battle against C. perfringens infection. Furthermore, the main objective of this in silico investigation is to design an MEV that targets C. perfringens. For this purpose, we selected the top three proteins that were highly antigenic using immuno-informatics approaches, including molecular docking. B-cells, IFN-gamma, and T cells for target proteins were predicted and the most conserved epitopes were selected for further investigation. For the development of the final MEV, epitopes of LBL5, CTL17, and HTL13 were linked to GPGPG, AAY, and KK linkers. The vaccine N-end was joined to an adjuvant through an EAAK linker to improve immunogenicity. After the attachment of linkers and adjuvants, the final construct was 415 amino acids. B-cell and IFN-gamma epitopes demonstrate that the model structure is enhanced for humoral and cellular immune responses. To validate the immunogenicity and safety of the final construct, various physicochemical properties, and other properties such as antigenicity and non-allergens, were evaluated. Furthermore, molecular docking was carried out for verification of vaccine compatibility with the receptor, evaluated in silico. Also, in silico cloning was employed for the verification of the proper expression and credibility of the construct.

scholarly journals Modeling Neuroimmune Interactions in Human Subjects and Animal Models to Predict Subtype-Specific Multidrug Treatments for Gulf War Illness

2021 ◽  
Vol 22 (16) ◽  
pp. 8546
Author(s):  
Francisco J. Carrera Arias ◽  
Kristina Aenlle ◽  
Maria Abreu ◽  
Mary A. Holschbach ◽  
Lindsay T. Michalovicz ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Human Subjects ◽  
Treatment Strategies ◽  
Gulf War ◽  
Clinical Samples ◽  
Stable States ◽  
Response Dynamics ◽  
Gulf War Illness ◽  
Bbb Permeability ◽  
The Brain

Gulf War Illness (GWI) is a persistent chronic neuroinflammatory illness exacerbated by external stressors and characterized by fatigue, musculoskeletal pain, cognitive, and neurological problems linked to underlying immunological dysfunction for which there is no known treatment. As the immune system and the brain communicate through several signaling pathways, including the hypothalamic–pituitary–adrenal (HPA) axis, it underlies many of the behavioral and physiological responses to stressors via blood-borne mediators, such as cytokines, chemokines, and hormones. Signaling by these molecules is mediated by the semipermeable blood–brain barrier (BBB) made up of a monocellular layer forming an integral part of the neuroimmune axis. BBB permeability can be altered and even diminished by both external factors (e.g., chemical agents) and internal conditions (e.g., acute or chronic stress, or cross-signaling from the hypothalamic–pituitary–gonadal (HPG) axis). Such a complex network of regulatory interactions that possess feed-forward and feedback connections can have multiple response dynamics that may include several stable homeostatic states beyond normal health. Here we compare immune and hormone measures in the blood of human clinical samples and mouse models of Gulf War Illness (GWI) subtyped by exposure to traumatic stress for subtyping this complex illness. We do this via constructing a detailed logic model of HPA–HPG–Immune regulatory behavior that also considers signaling pathways across the BBB to neuronal–glial interactions within the brain. We apply conditional interactions to model the effects of changes in BBB permeability. Several stable states are identified in the system beyond typical health. Following alignment of the human and mouse blood profiles in the context of the model, mouse brain sample measures were used to infer the neuroinflammatory state in human GWI and perform treatment simulations using a genetic algorithm to optimize the Monte Carlo simulations of the putative treatment strategies aimed at returning the ill system back to health. We identify several ideal multi-intervention strategies and potential drug candidates that may be used to treat chronic neuroinflammation in GWI.

scholarly journals The hermeneutics of mental symptoms in the Cambridge School

2015 ◽  
Vol 18 (4) ◽  
pp. 599-618 ◽  
Author(s):  
Massimiliano Aragona ◽  
Ivana S. Marková
Keyword(s):  
Natural Kinds ◽  
Therapeutic Interventions ◽  
Subjective Experiences ◽  
New Model ◽  
Mental Symptom ◽  
Cultural Information ◽  
Mental Symptoms ◽  
The Brain ◽  
Cambridge School ◽  
Symptom Formation

Current Psychiatry is in crisis. Decades of neuroscientific research have not yet delivered adequate explanations or treatments. One reason for this failure may be the wrongness of its central assumption, namely that mental symptoms and disorders are natural kinds. The Cambridge School has proposed that a new Epistemology must be constructed for Psychiatry, and that this should start with the development of a new model of mental symptom-formation. ‘Mental symptoms’ should be considered as hermeneutic co-constructions occurring in a intersubjective space created by the dialogue between sufferer and healer. Subjective experiences (caused either by neurobiological or psychosocial upheaval) penetrate the awareness of sufferers causing perplexity and/or distress. To understand, handle and communicate these experiences, sufferers proceed to configure them by means of templates borrowed from their own culture. Importantly, however, the same neurobiological information can be configured into different symptoms; and different neurobiological information into the same symptom. Therefore, ‘mental symptoms’ are dissimilar hybrid combinations of neurobiological and cultural information. To be ethical, therapeutic interventions must take into account such dissimilarities. Blind manipulation of the brain in all cases should be considered as counterproductive.

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